Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases

Immunology. 2022 Jan;165(1):3-21. doi: 10.1111/imm.13420. Epub 2021 Oct 5.

Abstract

An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self-antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme-coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases.

Keywords: autoimmune disease; channel kinase; inflammation; rheumatoid arthritis; transient receptor potential melastatin 7.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / therapy
  • Autoimmunity*
  • Biomarkers
  • Disease Susceptibility
  • Drug Development
  • Gene Expression Regulation / drug effects
  • Humans
  • Immune System / cytology
  • Immune System / drug effects
  • Immune System / immunology
  • Immune System / metabolism
  • Immunomodulation* / drug effects
  • Ion Channel Gating / drug effects
  • Organ Specificity / drug effects
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • TRPM Cation Channels / chemistry
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism*

Substances

  • Biomarkers
  • Protein Kinase Inhibitors
  • TRPM Cation Channels
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human